Table 2.
Combinations of bortezomib with other chemotherapeutic agents in relapsed and refractory disease
| Study drugs | Reference | No of assessable patients | Median no of prior regimes | Median no of cycles | Major response rate (CR+PR) | Response rates | Follow up | Toxicities | |
|---|---|---|---|---|---|---|---|---|---|
| Bortezomib Cyclophosphamide Dexamethasone | Phase II | Kropff et al 2005 | 50 | 2 | 6 | 76% | CR 10% PR 66% MR 12% | Median EFS 10 months | Neuropathy Infections, herpes zoster Thrombocytopenia Cardiovascular events |
| Bortezomib Cyclophosphamide Prednisolone | Phase I/II | Reece et al 2005 | 15 | All had at least 1 prior autograft | 2 patients completed | 31% | CR 6% PR 25% MR 25% | Not yet complete | Infections Hypophosphatemia Cytopenia |
| Bortezomib Thalidomide +/− Dexamethasone | Phase I/II | Zangari et al 2005 | 85 | 66% received 2 prior autografts | 2–12 cycles given | 71% | ≥n-CR 16% PR 55% MR 15% | Median OS/EFS9/22 months | Myelosuppression Neuropathy |
| Bortezomib +/− Methylprednisolone (weekly dosing) | Phase II | Suvannasankha and Smith 2005 | 28 | 70% prior autograft | 5 | 59% | CR 3% n-CR 3% PR 53% | Not yet complete | Neuropathy Gastrointestinal Congestive heart failure |
| Bortezomib Low dose Melphalan +/− Dexamethasone | Phase I/II | Popat et al 2005 | 16 | 3 | 4 | 50% ORR (75% with dex) | Median time to any response 1 cycle | Not yet complete | Neuropathy Myocardial infraction Thrombocytopenia Neutropenia |
| Bortezomib Melphalan | Phase I/II | Berenson et al 2006 | 34 | 3 | 15 patients completed 8 cycles | 47% | CR 6% n-CR 9% PR 32% MR 21% | Median free PFS 8 months | Myelosuppression Neuropathy Gastrointestinal |
| Bortezomib Melphalan Prednisolone Thalidomide | Phase II | Palumbo et al 2005 | 20 | 55% received 2 prior therapies | 3 | 50% | CR 10% n-CR 5% PR 35% MR 13% | Not yet complete | Thrombocytopenia Febrile neutropenia Herpes Zoster Neuropathy |
| Bortezomib Lenalidomide +/− Dexamethasone | Phase I | Richardson, Schlossman, et al 2005 | 17 | 7 | 4 | 59% | CR 6% n-CR 6% PR 47% MR 17% | Not yet complete | Thrombocytopenia Hyponatraemia Hypotension Fatigue |
| Bortezomib Pegylated liposomal doxorubicin (advanced hematological malignancies) | Phase I | Orlowski et al 2005 | 22 patients with myeloma | 5 (all patients) | 4 | 73% | CR 23% n-CR 14% PR 36% MR or stable disease 23% | Not yet complete | Myelosuppression Fatigu Pneumonia Neuropathy Diarrhea |
Abbreviations: CR, complete response; EFS, event free survival; MR, minor response; n-CR, near complete response; ORR, overall response rate (CR+PR+MR); OS, overall survival; PR, partial response; TTP, time to progression.